Kaposi's sarcoma-associated herpesvirus (KSHV), or human herpesvirus 8, is the etiologic agent of Kaposi's sarcoma (KS), and other proliferative disorders. KS was one of two sentinel diseases that heralded the AIDS epidemic, and KS remains a significant problem, particularly in areas, such as sub-Saharan Africa. There is limited therapy for KS, and as with all herpesviruses, a person is infected with KSHV for life. Currently there is no vaccine available for KSHV, but vaccination that could limit acquisition would be the best preventative measure. The objective of this proposal is to identify KSHV proteins that are antigens for human neutralizing antibodies, and CD4 T-cells, that could aid in the development of a vaccine to KSHV. The goals of this proposal include: A. Determination of the KSHV proteins that are targets for human neutralizing antibodies. B. Determine if a cell type dependent neutralization of KSHV by human NAb exists. C. Because much of KSHV transmission occurs via the oral cavity we want to determine if neutralizing antibodies are present in human saliva in response to a natural KSHV infection. D. To identify the KSHV proteins that are recognized by human CD4 T-cells, since they are directly linked to the development of an antibody response. PUBLIC HEALTH RELEVANCE: The objectives of this proposal are to identify KSHV proteins that are targets for neutralizing antibodies, and proteins that are recognized by CD4 T-cells. In the future these proteins could provide the basis for the development of vaccines to KSHV, and may also improve our understanding of the immunological control of herpesviruses.